Life-long dietary restrictions have negligible or damaging effects on late-life cognitive performance: A key role for genetics in outcomes.
Document Type
Article
Publication Date
10-2022
Publication Title
Neurobiology of aging
Keywords
JMG
JAX Source
Neurobiol Aging 2022 Oct; 118:108-116
Volume
118
First Page
108
Last Page
116
ISSN
1558-1497
PMID
35914473
DOI
https://doi.org/10.1016/j.neurobiolaging.2022.07.004
Grant
GM132006, AG054180, AG063755, AG059778, AG038070
Abstract
Several studies report that caloric restriction (CR) or intermittent fasting (IF) can improve cognition, while others report limited or no cognitive benefits. Here, we compare the effects of 20% CR, 40% CR, 1-day IF, and 2-day IF feeding paradigms to ad libitum controls on Y-maze working memory (WM) and contextual fear memory (CFM) in a large population of Diversity Outbred mice that model the genetic diversity of humans. While CR and IF interventions improve lifespan, we observed no enhancement of working memory or CFM in mice on these feeding paradigms, and report 40% CR to be damaging to recall of CFM. Using Quantitative Trait Loci mapping, we identified the gene Slc16a7 to be associated with CFM outcomes in aged mice on lifespan promoting feeding paradigms. Limited utility of dieting and fasting on memory in mice that recapitulate genetic diversity in the human population highlights the need for anti-aging therapeutics that promote cognitive function, with the neuronal monocarboxylate transporter MCT2 encoded by Slc16a7 highlighted as novel target.
Recommended Citation
Ouellette A,
Hadad N,
Deighan A,
Robinson L,
O'Connell K,
Freund A,
Churchill G,
Kaczorowski C.
Life-long dietary restrictions have negligible or damaging effects on late-life cognitive performance: A key role for genetics in outcomes. Neurobiol Aging 2022 Oct; 118:108-116